Thrombopoietin, also known as thrombopoietin, is understood by medicine to be a peptide that is active as a hormone and belongs to the cytokines. The glycoprotein is primarily involved in the formation of platelets in the bone marrow. Increased or decreased concentrations of the hormone in serum indicate hematopoietic disorders of various causes.
What is thrombopoietin?
Thrombopoietin is hormonal glycoprotein belonging to the group of cytokines. Cytokines are regulatory peptides. This makes them proteins implicated in the regulation of the immune response. Thrombopoietin is produced in the liver, in bone marrow stromal cells, in striated muscle and in the kidney. In human bone marrow, thrombopoietin stimulates the so-called megakaryocytes. These giant cells or blood stem cells are responsible for the formation of new cells in the blood and the immune system. Among other things, platelets are formed from the giant cells. The determination of the concentration of thrombopoietin in the blood can serve various diagnostic purposes, because this value says something about the number of platelets and megakaryocytes in the organism. Both unexpectedly high and unexpectedly low levels of thrombopoietin have disease value and may indicate, for example, inflammation and infection.
Anatomy and structure
Thrombopoietin is approximately 78 kDa in size and is one of the glycoproteins. Between 332 and 335 amino acids make up a thrombopoietin. The N-terminal domain of the peptide resembles erythropoietin, which is a hormone with similar regulatory functions in the formation of erythrocytes. Genetically, the gene of thrombopoietin is located on the longer arm of chromosome three at site q26.3-27. Its hormonal regulatory circuit distinguishes thrombopoietin from other hormones in that it involves the number of all available receptors in its control. Thrombopoietin promotes the formation of platelets, which in turn bind to the hormone in the blood via a thrombopoietin receptor on their surface. Thus, as the number of platelets formed decreases, the concentration of thrombopoietin in the blood decreases, and new platelet formation is down-regulated in this manner.
Function and Tasks
Especially for thrombopoiesis, the hormone thrombopoietin plays an important role. Thrombopoiesis occurs in the bone marrow and is the formation of platelets, which is counted as part of hematopoiesis. Blood clotting is dependent on thrombopoiesis, so that thrombopoietin, in the broadest sense, makes blood clotting possible in the first place and thus protects the body from major blood loss and infection in the event of injury. During thrombopoiesis in the bone marrow, platelets develop from mesenchymal cells, which in principle can become all blood cells and therefore belong to the stem cells. By developing into lymphoid and myeloid stem cells, the stem cell irreversibly decides to produce a certain series of cells. Myeloid stem cells develop into megakaryoblasts in the first step. Then they become megakaryocytes and in the last step they develop into platelets. Each platelet lives between five and twelve days and is eventually degraded in the spleen, lungs or liver. Therefore, thrombopoiesis must take place permanently in the bone marrow. The production of new platelets is stimulated by thrombopoietin, which is synthesized in organs such as the kidney and liver. Circulating platelets take up the hormone with their receptors and degrade it. Likewise, megakaryocytes proceed in contact with the peptide. The concentration of thrombopoietin in the blood is inversely proportional to the amount of megakaryocytes and platelets circulating in the blood. Thus, the lower the concentration of thrombopoietin, the higher the number of circulating platelets.
Diseases
Values that thrombopoietin can be used to estimate the number of platelets. In turn, the number of platelets can be used to detect many disorders of platelet topoiesis. For example, thrombocytopenia can be caused by such disorders. This is a deficiency of platelets. The physician speaks of thrombocytopenia only when there is a lower number than 150,000 platelets per µl of blood. The causes of such underproduction can be various. Acquired damage to the bone marrow, for example, should be considered. This includes, for example, damage caused by poisoning.Physical damage such as could be caused by chemotherapy is also sometimes the cause. The same applies to tumors. Folic acid and vitamin B12 deficiencies can also be causative. On the other hand, underproduction of thrombopoietin may also be responsible for low platelet levels due to damage to the liver. Congenital causes such as hematopoietic disorders in the context of a genetic syndrome can just as easily cause underproduction. Therapeutic treatments such as dialysis can reduce the number of platelets in the blood just as much. The same is true for medical devices such as heart valves, as they could mechanically damage platelets. Thrombocytosis is when there is excessive production of platelets. More than 500,000 platelets are found in one µl in this case. Such overproduction occurs after major blood loss and surgery. Tumors can also be causative. When there is a persistently high concentration of platelets, it is called essential thrombocythemia. This phenomenon is a malignant proliferation of platelets that is due to a genetic cause and should be counted among the neoplasms.
